2b or not 2b, when should there be an access lens on R&D?

We all know developing medicines is expensive (circa $2BN, if we consider the failures); time-consuming (10-13 years, from pre-clinical to launch) and with 16% of medicines having been withdrawn from the German market between 2011 and 2016 (after AMNOG assessment), it is not surprising that the focus on Access is high and increasing.  

In addition to Health Technology Assessment (HTA) ‘failures’, what we spend less time quantifying, as an Industry, is the partial successes that pass regulatory and HTA and then fail in the competitive landscape. Over the last decades, an increasing number of pharma companies have sought to address both these challenges by bringing commercial ‘oversight’ (usually an Access lens) into the R&D process. 

This oversight is usually pulsed and targeted to key stage gates where it can best serve the R&D process – allowing customer/ patient/payer-facing roles the opportunity to collaborate with the development team. The voice of the patient can be amplified and so too can the payer's need – the premise being that this can only improve a medicine’s probability of success. 

The challenge faced by many clinical teams is to bring a medicine to market (or in reality, often to the USA market) as quickly as possible (and within budget). Success in the US can define any company (and it is usually the shareholder focus) but obviously, most of the world’s population lies elsewhere. The trick to this collaborative approach is to identify what can be accomplished within the clinical team’s goals.  

At Decisive Consulting we have had decades of experience in supporting the R&D process and this article discusses some of the ‘wins’ that a truly collaborative approach can have. The following are anonymised extracts from our tapestry of experiences  

Patient Population 

It may surprise the reader that the patient population can be debated at phase IIb – this is surprisingly common and not just related to HTA considerations. One of the reasons that this can happen is that the science (driving the medicinal development) may support a low-risk scientific strategy against a milder form of the disease, but the unmet need is in the moderate to severe form of the disease.  

Other reasons that the patient population may be challenged are varied: 

• There may be a fast-to-market (orphan?) indication that would allow speedier access 
• It could be that the formulation developed is typically positioned for a different sub-population. For example, IV is rarely used in mild forms of a disease, if the competitors are all oral in mild and IV in severe it may be prudent to look at the target segment again if planning IV for mild. Nothing is binary – there may be a good reason, but it is important to check 
• It may be that the treatment algorithm is looking very crowded by the time of the planned launch (i.e. limited unmet need in the future) and a tactical side-step into a different stage/ population on the algorithm could create a different opportunity. It may be that a respected competitor has side-stepped and then the question is should we follow? 

The patient segment needs to match the “who” to the “why” and to do so consideration of the disease, data, treatment protocols and competitor landscape is important.  

Endpoints 

This is often the most difficult area to navigate. Much is driven by regulatory and statistical requirements but there can be opportunities to add value. 

In an Advisory Board, discussing phase IIb data – a KOL mooted that he had used a different scale in a publication and asked if we had considered that – we had not. It worked retrospectively but then the question is, do we take it into phase III? Safer, perhaps, to have tested and validated it prospectively in phase IIb. 

This is when the team dynamic really can shine – often it is the clinical and stats team members that can support other colleagues and solution find. Even exploratory additions to the statistical analysis plan are challenging without their buy-in and engagement. 

Comparator 

Often US studies are placebo-controlled but where there is a comparator it is worth a discussion to understand which could be considered global viable options – sometimes a path can be found that works for the US and beyond. Sometimes it cannot. Physician choice is a viable option but often slows studies and increases costs and interpretation significantly. 

In placebo-controlled studies, capturing and documenting failed therapies can help considerably in the HTA assessment. 

Where there is no direct comparator, it may be prudent to map out how an Indirect Treatment Comparator analysis could be optimised ahead of time. For example: minimising heterogeneity of the patients/ baseline characteristics, consistent methods used etc all increase the acceptance/ robustness of the ITC. However, ITCs are not universally accepted, and it is worth noting that even Germany’s IQWIG) Institute for Quality and Efficiency in Health Care did not accept 84% of ITCs in May 2019 – citing use of unadjusted comparisons and a lack of data to support the ITC. 

Supportive data can also be generated appropriately in Early Access Programmes (EAP) – a lot depends on how the EAP was set up and in which countries it was conducted to understand the opportunity. 

Cost of Goods 

Whilst not necessarily a tale for Clinical, this is an important theme which raises its head more often than you may expect within a New Chemical Entity development team. 

A development team, during a workshop, realised we may have a cost of goods challenge. The early price assessment meant it was highly likely that the cost of goods would be higher than the likely selling price (in EU and beyond). After much discussion significant efforts were put into the plan to reduce cost of goods to ensure an acceptable margin – if this had been identified at Phase III it would have been too late and a product launch ex US may never have happened.  

A stitch in time… 

Whilst one could argue the earlier the better (to bring an extended team together to review the development plan) it is rare that an early intervention can add significant value. Candidate selection discussions can be very much Target Product Profile driven knowing that directionally they are in the ballpark.  

Once data is being generated and the extended team has begun to understand the patient journey, disease, competitive landscape with greater surety then the investment of bringing the extended team together can yield dividends. 

We believe that the optimum timing for the cross-functional team to deep dive into the development plan is 2b although there are opportunities to course correct later. The value in diving into the program too early is moot and may mean the advice is, at best, woolly and lacking direction. 

We believe strategy without access will not deliver breakthrough medicines to patients, no matter how tremendous the promise is. We approach Commercial Strategy with an “access first” lens and work to break down unnecessary silos. Making sure patients can ultimately get access is everyone’s business. We have created a workshop offering that can navigate cross-functional development teams through a series of questions. The output is a team that understands the strategy and any trade-offs; a team that understands any planned mitigations and looks to address them thereby increasing the likelihood of a successful HTA and broader access. 

Click on the link to arrange a short call/ find out more.